Infectious human immunodeficiency virus type-1 (HIV) has been identified int he cervico-vaginal secretions and semen of HIV infected individuals. In both North America and Europe heterosexual intercourse is currently the mode of HIV transmission with the fastest rising incidence. Further, it has been shown in the simian immunodeficiency virus (SIV) model of AIDS that the application of cell-free virus particles of virus infected lymphocytes to either the vaginal or urethral mucosal transmits infection. Thus, has become clear that HIV is predominantly a sexually transmitted disease, and that effective prophylactics vaccination will require that immunity be induced at the genitourinary mucosa. Systemic immunization is rarely effective in this respect, and mucosal immunity is most often achieved through direct immunization of mucosally- associated lymphoid tissues of the gut and respiratory tract. Previous studies by this group showed that female macaques which were systematically primed and mucosally boosted with whole inactivated SIV vaccine in biodegradable microsphere exhibited specific antibodies in their cervico-vaginal secretions and resisted vaginal challenge. The overall goal of the CMIG effort will be extend these studies to the protection of males with defined vaccine antigens. In this component of the CMIG, SIV, and HIV virus-like particles of males with defined vaccine antigens. In this component of the CMIG, SIV and HIV virus-like particles recombinant SIV gp 130 and SIV and HIV DNA expression vectors will be microencapsulated and immunologically evaluated in mice so that the most promising vaccine formulations and immunization strategies can be advanced into the male urethral challenge model. Immune sera and mucosal secretions from the mice and macaques will be evaluated for their levels of IgM, IgG and IgA anti-SIV/HIV antibodies by ELISA and western blot analysis. ELISPOP assays will be used to quantitate the number and isotype distribution of specific antibody-secreting cells in the spleens and gut lamina propria of mice and the blood mononuclear cells of macaques. In addition, virus-specific cytotoxic T cell responses by the spleen and gut intraepithelial lymphocytes and macaque blood mononuclear cells will be quantitated. The specific objective of this component of the CMIG is to immunologically evaluate immunization approaches with vaccine antigens that the most promising can be selectively advanced to the male macaque urethral challenge model.